Preventing oxidative stress in rats with aldosteronism by calcitriol and dietary calcium and magnesium supplements

Background: Prominent features of the clinical syndrome of congestive heart failure (CHF) include alclosteronism and the presence of oxidative stress. Secondary hyperparathyroidism (SHPT) accompanies aldosteronism due to increased urinary and fecal excretion of a. SHPT accounts for intracellular Ca2+ overloading of diverse cells, including peripheral blood mononuclear cells (PBMC), and the appearance of oxidative stress. Parathyroidectomy or a Ca2+ channel blocker each prevent these responses. Herein, we hypothesized calcitriol, or 1,25(OH)(2)D-3, plus a diet supplemented with Ca2+ and Mg2+ (CMD) would prevent SHPT and Ca2+ overloading of PBMC and thereby oxidative stress in these cells in rats receiving aldosterone/salt treatment (ALDOST). Methods and Results: In rats with ALDOST for 4 weeks, without or with CMD, we monitored plasma-ionized [Ca2+](o) and parathyroid hormone (PTH), and PBMC cytosolic-free [Ca2+](i) and H2O2 production. Untreated, age- and gender-matched rats served as controls. Compared to controls, ALDOST led to an expected fall in plasma [Ca2+] level with accompanying rise in plasma PTH level and intracellular Ca2+ overloading of PBMC and their increased production of H2O2. CMD prevented SHPT and abrogated intracellular Ca2+ overloading of PBMC and their increased H2O2 production. Conclusions: The appearance of SHPT in aldosteronism, induced by fallen plasma [Ca2+], leads to PTH-mediated Ca2+ overloading of PBMC and their increased production of H2O2, SHPT in rats with aldosteronism can be prevented by calcitriol and a diet supplemented with Ca2+ and Mg2+. These findings raise the prospect that the SHPT found in CHF could be managed with macro- and micronutrients.